Alpha interferons are used widely for the treatment of a variety of hematological malignancies including hairy cell leukemia, chronic myelogenous leukemia, low grade lymphomas, cutaneous T-cell lymphomas, and solid tumors such as renal cell carcinoma, melanoma, carcinoid tumors and AIDS-related Kaposi's sarcoma (Gutterman, J. U., Proc. Natl. Acad Sci. USA, 1994 91: 1198-1205). Antitumor effects are usually seen at high dosage levels, often of the order of tens of millions of units of interferon-.alpha. (IFN-.alpha.), administered by parenteral injection. Interferon-.alpha. is a Type I interferon, a class which also includes the .beta. and .omega. interferons. Although a number of routes of administration, including intravenous, subcutaneous, intramuscular, topical, and intralesional injection, are commonly employed for the administration of type I interferons, the oral route has not been generally used, because interferons are proteins which are considered to be inactivated by proteolytic enzymes and which are not absorbed appreciably in their native form in the gastrointestinal tract. Indeed a number of studies have failed to detect interferons in the blood following oral administration (Cantell and Pyhala, J. Gen. Virol., 1973 20: 97-104; Wills et al, J. IFN Res., 1984 4: 399-409; Gilson et al, J. IFN Res., 1985 5: 403-408).
There have been a number of anecdotal reports of efficacy of low doses of interferon administered as a nasal spray or as an oral liquid formulation in the treatment of a variety of conditions, particularly influenza. A series of patent specifications has described the use of low doses of orally administered interferon of heterologous species origin for the treatment of infectious rhinotracheitis ("shipping fever") in cattle, and of feline leukemia, and also treatment of other conditions, for enhancement of efficiency of vaccines; for improving the efficiency of food utilization; and for prevention of bovine theileriosis. See U.S. Pat. No. 4,462,985, Australian Patent No. 608519, Australian Patent No. 583332 and U.S. Pat. No. 5,215,741 respectively. In addition U.S. Pat. No. 5,017,371 discloses the use of interferon in this way for treatment of side-effects of cancer chemotherapy or radiotherapy. In these specifications, the interferon used was human interferon-.alpha. prepared by the method of Cantell, administered in phosphate buffered saline, at a dose of 0.01 to 5 IU per pound body weight. While these specifications suggest that such low doses of interferon administered to the oropharyngeal mucosa, preferably in a form adapted for prolonged contact with the oral mucosa, may be efficacious for treatment of a wide variety of conditions including cancer, the experimental evidence for conditions other than shipping fever, feline leukemia, canine parvovirns and theileriosis is largely anecdotal. In particular, no properly controlled trials of this treatment in any animal model for human cancers are presented.
In contrast, the invention disclosed herein is based upon the first controlled study in an animal model of the efficacy of oromucosally administered interferon for the treatment of neoplastic diseases.